ID RPGF4_HUMAN Reviewed; 1011 AA. AC Q8WZA2; B2R7R3; B7Z283; B7Z3T6; B7Z912; O95636; Q8IXK6; Q8TAA4; DT 20-JUN-2003, integrated into UniProtKB/Swiss-Prot. DT 01-MAR-2002, sequence version 1. DT 24-JAN-2024, entry version 181. DE RecName: Full=Rap guanine nucleotide exchange factor 4; DE AltName: Full=Exchange factor directly activated by cAMP 2; DE AltName: Full=Exchange protein directly activated by cAMP 2; DE Short=EPAC 2; DE AltName: Full=cAMP-regulated guanine nucleotide exchange factor II; DE Short=cAMP-GEFII; GN Name=RAPGEF4; Synonyms=CGEF2, EPAC2; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND FUNCTION. RX PubMed=9856955; DOI=10.1126/science.282.5397.2275; RA Kawasaki H., Springett G.M., Mochizuki N., Toki S., Nakaya M., Matsuda M., RA Housman D.E., Graybiel A.M.; RT "A family of cAMP-binding proteins that directly activate rap1."; RL Science 282:2275-2279(1998). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), AND ALTERNATIVE PROMOTER RP USAGE. RX PubMed=11707077; DOI=10.1006/geno.2001.6641; RA Ueno H., Shibasaki T., Iwanaga T., Takahashi K., Yokoyama Y., Liu L.M., RA Yokoi N., Ozaki N., Matsukura S., Yano H., Seino S.; RT "Characterization of the gene EPAC2: structure, chromosomal localization, RT tissue expression, and identification of the liver-specific isoform."; RL Genomics 78:91-98(2001). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 3; 4 AND 5). RC TISSUE=Amygdala, Hippocampus, Thalamus, and Trachea; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., RA Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 and RT 4."; RL Nature 434:724-731(2005). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3). RC TISSUE=Hypothalamus, and Testis; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP FUNCTION. RX PubMed=10777494; DOI=10.1074/jbc.m001113200; RA de Rooij J., Rehmann H., van Triest M., Cool R.H., Wittinghofer A., RA Bos J.L.; RT "Mechanism of regulation of the Epac family of cAMP-dependent RapGEFs."; RL J. Biol. Chem. 275:20829-20836(2000). CC -!- FUNCTION: Guanine nucleotide exchange factor (GEF) for RAP1A, RAP1B and CC RAP2A small GTPases that is activated by binding cAMP. Seems not to CC activate RAB3A. Involved in cAMP-dependent, PKA-independent exocytosis CC through interaction with RIMS2 (By similarity). {ECO:0000250, CC ECO:0000269|PubMed:10777494, ECO:0000269|PubMed:9856955}. CC -!- SUBUNIT: Interacts with RIMS1 and RIMS2. Probably part of a complex CC with RIMS2 and GTP-activated RAB3A (By similarity). {ECO:0000250}. CC -!- INTERACTION: CC Q8WZA2; Q96MC5: BMERB1; NbExp=4; IntAct=EBI-948476, EBI-718468; CC Q8WZA2; Q9H4E7: DEF6; NbExp=3; IntAct=EBI-948476, EBI-745369; CC Q8WZA2; P42858: HTT; NbExp=3; IntAct=EBI-948476, EBI-466029; CC Q8WZA2; P05455: SSB; NbExp=3; IntAct=EBI-948476, EBI-358037; CC Q8WZA2; Q9UH65: SWAP70; NbExp=4; IntAct=EBI-948476, EBI-310749; CC Q8WZA2; P49459: UBE2A; NbExp=3; IntAct=EBI-948476, EBI-2339348; CC Q8WZA2-3; P54253: ATXN1; NbExp=3; IntAct=EBI-25977442, EBI-930964; CC -!- SUBCELLULAR LOCATION: Cytoplasm. Membrane {ECO:0000250}; Peripheral CC membrane protein {ECO:0000250}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative promoter usage, Alternative splicing; Named isoforms=5; CC Name=1; CC IsoId=Q8WZA2-1; Sequence=Displayed; CC Name=2; CC IsoId=Q8WZA2-2; Sequence=VSP_007611; CC Name=3; CC IsoId=Q8WZA2-3; Sequence=VSP_007612, VSP_007613; CC Name=4; CC IsoId=Q8WZA2-4; Sequence=VSP_054423; CC Name=5; CC IsoId=Q8WZA2-5; Sequence=VSP_054423, VSP_054424; CC -!- TISSUE SPECIFICITY: Predominantly expressed in brain and adrenal gland. CC Isoform 2 is expressed in liver. Isoform 1 is expressed in liver at CC very low levels. CC -!- DOMAIN: The N-terminal nucleotide phosphate binding region cAMP 1 has a CC much lower affinity for cAMP as compared to cAMP 2. CC -!- DOMAIN: The DEP domain is involved in membrane localization independent CC from regulation by cAMP. {ECO:0000250}. CC -!- MISCELLANEOUS: [Isoform 1]: Produced by alternative promoter usage. CC Promoter analysis was carried out in mouse. CC -!- MISCELLANEOUS: [Isoform 2]: Produced by alternative promoter usage. CC Promoter analysis was carried out in mouse. {ECO:0000305}. CC -!- MISCELLANEOUS: [Isoform 3]: Produced by alternative splicing of isoform CC 1. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U78516; AAD03422.1; -; mRNA. DR EMBL; AB027471; BAB72179.1; -; mRNA. DR EMBL; AK294445; BAH11769.1; -; mRNA. DR EMBL; AK296340; BAH12322.1; -; mRNA. DR EMBL; AK304278; BAH14148.1; -; mRNA. DR EMBL; AK313084; BAG35910.1; -; mRNA. DR EMBL; AK316072; BAH14443.1; -; mRNA. DR EMBL; AC009484; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC018712; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC019046; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC104086; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC024004; AAH24004.1; -; mRNA. DR EMBL; BC040183; AAH40183.1; -; mRNA. DR CCDS; CCDS42775.1; -. [Q8WZA2-1] DR CCDS; CCDS42776.1; -. [Q8WZA2-3] DR CCDS; CCDS63060.1; -. [Q8WZA2-4] DR CCDS; CCDS63061.1; -. [Q8WZA2-5] DR RefSeq; NP_001093867.1; NM_001100397.1. [Q8WZA2-3] DR RefSeq; NP_001269828.1; NM_001282899.1. [Q8WZA2-4] DR RefSeq; NP_001269829.1; NM_001282900.1. [Q8WZA2-5] DR RefSeq; NP_001269830.1; NM_001282901.1. DR RefSeq; NP_008954.2; NM_007023.3. [Q8WZA2-1] DR RefSeq; XP_006712268.1; XM_006712205.3. [Q8WZA2-5] DR AlphaFoldDB; Q8WZA2; -. DR SMR; Q8WZA2; -. DR BioGRID; 116253; 19. DR IntAct; Q8WZA2; 15. DR STRING; 9606.ENSP00000380271; -. DR BindingDB; Q8WZA2; -. DR ChEMBL; CHEMBL2029198; -. DR GuidetoPHARMACOLOGY; 1293; -. DR iPTMnet; Q8WZA2; -. DR PhosphoSitePlus; Q8WZA2; -. DR BioMuta; RAPGEF4; -. DR DMDM; 32171491; -. DR jPOST; Q8WZA2; -. DR MassIVE; Q8WZA2; -. DR PaxDb; 9606-ENSP00000380271; -. DR PeptideAtlas; Q8WZA2; -. DR ProteomicsDB; 6419; -. DR ProteomicsDB; 6544; -. DR ProteomicsDB; 75243; -. [Q8WZA2-1] DR ProteomicsDB; 75244; -. [Q8WZA2-2] DR ProteomicsDB; 75245; -. [Q8WZA2-3] DR Antibodypedia; 3825; 198 antibodies from 33 providers. DR DNASU; 11069; -. DR Ensembl; ENST00000397081.8; ENSP00000380271.3; ENSG00000091428.18. [Q8WZA2-1] DR Ensembl; ENST00000397087.7; ENSP00000380276.3; ENSG00000091428.18. [Q8WZA2-3] DR Ensembl; ENST00000538974.5; ENSP00000440135.1; ENSG00000091428.18. [Q8WZA2-5] DR Ensembl; ENST00000540783.5; ENSP00000440250.1; ENSG00000091428.18. [Q8WZA2-4] DR GeneID; 11069; -. DR KEGG; hsa:11069; -. DR MANE-Select; ENST00000397081.8; ENSP00000380271.3; NM_007023.4; NP_008954.2. DR UCSC; uc002uhv.5; human. [Q8WZA2-1] DR AGR; HGNC:16626; -. DR CTD; 11069; -. DR DisGeNET; 11069; -. DR GeneCards; RAPGEF4; -. DR HGNC; HGNC:16626; RAPGEF4. DR HPA; ENSG00000091428; Tissue enriched (brain). DR MIM; 606058; gene. DR neXtProt; NX_Q8WZA2; -. DR OpenTargets; ENSG00000091428; -. DR PharmGKB; PA134861108; -. DR VEuPathDB; HostDB:ENSG00000091428; -. DR eggNOG; KOG2378; Eukaryota. DR GeneTree; ENSGT00940000156075; -. DR InParanoid; Q8WZA2; -. DR OMA; LYCYVLE; -. DR OrthoDB; 5473909at2759; -. DR PhylomeDB; Q8WZA2; -. DR TreeFam; TF313184; -. DR PathwayCommons; Q8WZA2; -. DR Reactome; R-HSA-354192; Integrin signaling. DR Reactome; R-HSA-381676; Glucagon-like Peptide-1 (GLP1) regulates insulin secretion. DR Reactome; R-HSA-392517; Rap1 signalling. DR Reactome; R-HSA-422356; Regulation of insulin secretion. DR SignaLink; Q8WZA2; -. DR SIGNOR; Q8WZA2; -. DR BioGRID-ORCS; 11069; 7 hits in 1146 CRISPR screens. DR ChiTaRS; RAPGEF4; human. DR GeneWiki; RAPGEF4; -. DR GenomeRNAi; 11069; -. DR Pharos; Q8WZA2; Tchem. DR PRO; PR:Q8WZA2; -. DR Proteomes; UP000005640; Chromosome 2. DR RNAct; Q8WZA2; Protein. DR Bgee; ENSG00000091428; Expressed in right frontal lobe and 170 other cell types or tissues. DR ExpressionAtlas; Q8WZA2; baseline and differential. DR GO; GO:0005829; C:cytosol; IEA:Ensembl. DR GO; GO:0098686; C:hippocampal mossy fiber to CA3 synapse; IEA:Ensembl. DR GO; GO:0016020; C:membrane; TAS:ProtInc. DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central. DR GO; GO:0030552; F:cAMP binding; ISS:UniProtKB. DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; EXP:Reactome. DR GO; GO:0030674; F:protein-macromolecule adaptor activity; IEA:Ensembl. DR GO; GO:0031267; F:small GTPase binding; ISS:UniProtKB. DR GO; GO:0002250; P:adaptive immune response; TAS:Reactome. DR GO; GO:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; IEA:Ensembl. DR GO; GO:0017156; P:calcium-ion regulated exocytosis; IEA:Ensembl. DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; TAS:ProtInc. DR GO; GO:0030073; P:insulin secretion; IEA:Ensembl. DR GO; GO:0032024; P:positive regulation of insulin secretion; IEA:Ensembl. DR GO; GO:0007265; P:Ras protein signal transduction; IBA:GO_Central. DR GO; GO:0017157; P:regulation of exocytosis; IEA:Ensembl. DR GO; GO:0098693; P:regulation of synaptic vesicle cycle; IEA:Ensembl. DR CDD; cd00038; CAP_ED; 2. DR CDD; cd04437; DEP_Epac; 1. DR CDD; cd00155; RasGEF; 1. DR CDD; cd06224; REM; 1. DR Gene3D; 1.10.8.1240; -; 1. DR Gene3D; 2.60.120.10; Jelly Rolls; 2. DR Gene3D; 1.10.840.10; Ras guanine-nucleotide exchange factors catalytic domain; 1. DR Gene3D; 1.20.870.10; Son of sevenless (SoS) protein Chain: S domain 1; 1. DR Gene3D; 1.10.10.10; Winged helix-like DNA-binding domain superfamily/Winged helix DNA-binding domain; 1. DR InterPro; IPR000595; cNMP-bd_dom. DR InterPro; IPR018490; cNMP-bd_dom_sf. DR InterPro; IPR000591; DEP_dom. DR InterPro; IPR008937; Ras-like_GEF. DR InterPro; IPR000651; Ras-like_Gua-exchang_fac_N. DR InterPro; IPR019804; Ras_G-nucl-exch_fac_CS. DR InterPro; IPR023578; Ras_GEF_dom_sf. DR InterPro; IPR001895; RASGEF_cat_dom. DR InterPro; IPR036964; RASGEF_cat_dom_sf. DR InterPro; IPR014710; RmlC-like_jellyroll. DR InterPro; IPR029071; Ubiquitin-like_domsf. DR InterPro; IPR036388; WH-like_DNA-bd_sf. DR InterPro; IPR036390; WH_DNA-bd_sf. DR PANTHER; PTHR23113; GUANINE NUCLEOTIDE EXCHANGE FACTOR; 1. DR PANTHER; PTHR23113:SF175; RAP GUANINE NUCLEOTIDE EXCHANGE FACTOR 4; 1. DR Pfam; PF00027; cNMP_binding; 2. DR Pfam; PF00610; DEP; 1. DR Pfam; PF00617; RasGEF; 1. DR Pfam; PF00618; RasGEF_N; 1. DR PRINTS; PR00103; CAMPKINASE. DR SMART; SM00100; cNMP; 2. DR SMART; SM00049; DEP; 1. DR SMART; SM00147; RasGEF; 1. DR SMART; SM00229; RasGEFN; 1. DR SUPFAM; SSF51206; cAMP-binding domain-like; 2. DR SUPFAM; SSF48366; Ras GEF; 1. DR SUPFAM; SSF54236; Ubiquitin-like; 1. DR SUPFAM; SSF46785; Winged helix' DNA-binding domain; 1. DR PROSITE; PS50042; CNMP_BINDING_3; 2. DR PROSITE; PS50186; DEP; 1. DR PROSITE; PS00720; RASGEF; 1. DR PROSITE; PS50009; RASGEF_CAT; 1. DR PROSITE; PS50212; RASGEF_NTER; 1. DR Genevisible; Q8WZA2; HS. PE 1: Evidence at protein level; KW Alternative promoter usage; Alternative splicing; cAMP; cAMP-binding; KW Cytoplasm; Exocytosis; Guanine-nucleotide releasing factor; Membrane; KW Nucleotide-binding; Reference proteome; Repeat. FT CHAIN 1..1011 FT /note="Rap guanine nucleotide exchange factor 4" FT /id="PRO_0000068870" FT DOMAIN 216..291 FT /note="DEP" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00066" FT DOMAIN 496..634 FT /note="N-terminal Ras-GEF" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00135" FT DOMAIN 772..1009 FT /note="Ras-GEF" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00168" FT BINDING 422..425 FT /ligand="3',5'-cyclic AMP" FT /ligand_id="ChEBI:CHEBI:58165" FT /evidence="ECO:0000250|UniProtKB:O95398" FT BINDING 432..433 FT /ligand="3',5'-cyclic AMP" FT /ligand_id="ChEBI:CHEBI:58165" FT /evidence="ECO:0000250|UniProtKB:O95398" FT VAR_SEQ 1..315 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:11707077" FT /id="VSP_007611" FT VAR_SEQ 1..153 FT /note="Missing (in isoform 4 and isoform 5)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_054423" FT VAR_SEQ 1..144 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15489334" FT /id="VSP_007612" FT VAR_SEQ 145..148 FT /note="ALWE -> MLYK (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15489334" FT /id="VSP_007613" FT VAR_SEQ 180..197 FT /note="Missing (in isoform 5)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_054424" FT CONFLICT 324 FT /note="P -> R (in Ref. 5; AAH40183)" FT /evidence="ECO:0000305" FT CONFLICT 511 FT /note="H -> R (in Ref. 5; AAH40183)" FT /evidence="ECO:0000305" FT CONFLICT 647 FT /note="L -> I (in Ref. 5; AAH40183)" FT /evidence="ECO:0000305" FT CONFLICT 679 FT /note="H -> P (in Ref. 5; AAH24004)" FT /evidence="ECO:0000305" FT CONFLICT 732 FT /note="T -> M (in Ref. 5; AAH24004)" FT /evidence="ECO:0000305" FT CONFLICT 873 FT /note="V -> I (in Ref. 1; AAD03422)" FT /evidence="ECO:0000305" FT CONFLICT 902 FT /note="P -> T (in Ref. 5; AAH40183)" FT /evidence="ECO:0000305" SQ SEQUENCE 1011 AA; 115522 MW; 9427C5F92F2FFAD1 CRC64; MVAAHAAHSS SSAEWIACLD KRPLERSSED VDIIFTRLKE VKAFEKFHPN LLHQICLCGY YENLEKGITL FRQGDIGTNW YAVLAGSLDV KVSETSSHQD AVTICTLGIG TAFGESILDN TPRHATIVTR ESSELLRIEQ KDFKALWEKY RQYMAGLLAP PYGVMETGSN NDRIPDKENT PLIEPHVPLR PANTITKVPS EKILRAGKIL RNAILSRAPH MIRDRKYHLK TYRQCCVGTE LVDWMMQQTP CVHSRTQAVG MWQVLLEDGV LNHVDQEHHF QDKYLFYRFL DDEHEDAPLP TEEEKKECDE ELQDTMLLLS QMGPDAHMRM ILRKPPGQRT VDDLEIIYEE LLHIKALSHL STTVKRELAG VLIFESHAKG GTVLFNQGEE GTSWYIILKG SVNVVIYGKG VVCTLHEGDD FGKLALVNDA PRAASIVLRE DNCHFLRVDK EDFNRILRDV EANTVRLKEH DQDVLVLEKV PAGNRASNQG NSQPQQKYTV MSGTPEKILE HFLETIRLEA TLNEATDSVL NDFIMMHCVF MPNTQLCPAL VAHYHAQPSQ GTEQEKMDYA LNNKRRVIRL VLQWAAMYGD LLQEDDVSMA FLEEFYVSVS DDARMIAALK EQLPELEKIV KQISEDAKAP QKKHKVLLQQ FNTGDERAQK RQPIRGSDEV LFKVYCMDHT YTTIRVPVAT SVKEVISAVA DKLGSGEGLI IVKMSSGGEK VVLKPNDVSV FTTLTINGRL FACPREQFDS LTPLPEQEGP TVGTVGTFEL MSSKDLAYQM TIYDWELFNC VHELELIYHT FGRHNFKKTT ANLDLFLRRF NEIQFWVVTE ICLCSQLSKR VQLLKKFIKI AAHCKEYKNL NSFFAIVMGL SNVAVSRLAL TWEKLPSKFK KFYAEFESLM DPSRNHRAYR LTVAKLEPPL IPFMPLLIKD MTFTHEGNKT FIDNLVNFEK MRMIANTART VRYYRSQPFN PDAAQANKNH QDVRSYVRQL NVIDNQRTLS QMSHRLEPRR P //